Total Synthesis of Lobatamides A and C

The total synthesis of lobatamides A (1a) and C (1c) via a common bislactone intermediate is reported. The allylic aryl moiety including a trisubstituted Z‐olefin is constructed by hydroboration of 1,1‐disubstituted allene and subsequent Migita‐Kosugi‐Stille coupling. Although the seco acid proved to be highly unstable even in the presence of weak bases, Zhao macrolactonization under acidic conditions via the a‐acyloxyenamide successfully provided the common bislactone intermediate. Hydrozirconation‐iodination of the terminal alkyne and subsequent copper‐mediated coupling with primary amides successfully proceeded in the presence of the sensitive bislactone framework. The developed synthetic route enables the late‐stage installation of enamide side chains, which are crucial structures for V‐ATPase inhibitions.